Familial adenomatous polyposis (FAP) is one of those “don’t-miss” GI genetics topics because the testable concept is simple: lots of polyps + early colon cancer unless you intervene. If you can recognize the inheritance pattern, the gene, the extracolonic clues, and the screening/management pathway, you’ve basically locked the question.
The one-liner (what you should blurt out on test day)
FAP = autosomal dominant APC mutation → hundreds to thousands of adenomatous colon polyps in adolescence → near-100% colorectal cancer risk by ~age 40 if untreated (prophylactic colectomy).
Visual mnemonic (quick and sticky)
“APC = A Polyps Catastrophe”
Picture a colon flooded with polyps like popcorn:
- A = Autosomal dominant
- P = Polyps (hundreds–thousands)
- C = Cancer is coming (near inevitable without colectomy)
Extra hooks:
- “APC controls β-catenin” → when APC is lost, β-catenin accumulates → transcription of proliferative genes.
Core pathophysiology (high yield)
Gene + pathway
- Gene: APC tumor suppressor (chromosome 5q)
- Pathway: Wnt/β-catenin
- Normal: APC helps degrade β-catenin
- Mutated APC: β-catenin builds up → increased transcription (e.g., MYC, cyclin D) → adenoma formation
- Classic “two-hit” logic: Inherited one mutant allele, second hit occurs somatically → polyps/cancer
Hallmark clinical picture
Colon findings
- Hundreds to thousands of adenomatous polyps
- Often appear in teen years
- Colorectal cancer risk approaches 100% without intervention (often by age ~40)
Symptoms (when they show up)
- May be asymptomatic early
- Later: hematochezia, iron deficiency anemia, diarrhea, abdominal pain
Extracolonic associations (Step 1/2 favorites)
| Association | What to remember | Why it matters |
|---|---|---|
| Duodenal/periampullary adenomas | Major source of morbidity/mortality even after colectomy | Still need upper GI surveillance |
| Desmoid tumors | Fibrous tumors, often intra-abdominal; can be aggressive locally | Can complicate surgery and cause obstruction |
| Osteomas (skull/mandible) | Part of Gardner phenotype | Clue in stem |
| Congenital hypertrophy of retinal pigment epithelium (CHRPE) | Benign retinal lesions | “Weird eye finding” = points to FAP |
| Epidermoid cysts/dental abnormalities | Gardner spectrum | Another stem clue |
| Hepatoblastoma (kids) | Increased risk | Pediatric association (less common but testable) |
| Thyroid cancer (papillary) | Increased risk | May warrant screening in some protocols |
Variants you should recognize
- Gardner syndrome = FAP + osteomas + epidermoid cysts + desmoid tumors
- Turcot syndrome (APC-related variant) = FAP + CNS tumors (classically medulloblastoma)
Diagnosis: how it’s made (and how questions are written)
When to suspect
- Strong family history of early colon cancer
- Teen/young adult with many adenomatous polyps
- Extracolonic clues (desmoids, osteomas, CHRPE)
Confirmation
- Colonoscopy: numerous adenomatous polyps
- Genetic testing for APC mutation (also for at-risk relatives)
Screening & management (Step 2 clinical decision-making)
Key principle
Surveillance is not enough once polyp burden is significant—cancer risk is too high, so definitive prevention is surgical.
Typical approach (high yield)
- Start colon screening in at-risk patients: often early adolescence (timing varies by guideline, but Step-style questions expect “early and regular”).
- Definitive prevention: prophylactic colectomy
- Options include total proctocolectomy with ileal pouch-anal anastomosis or colectomy with ileorectal anastomosis (depends on rectal involvement/polyp burden).
After colectomy
- Still need:
- Upper endoscopy surveillance for duodenal/periampullary adenomas
- Monitoring for desmoid tumors
- NSAIDs (e.g., sulindac, celecoxib) can reduce polyp burden but do not replace surgery (common trick).
Differentials you’ll confuse with FAP (sort them fast)
| Disorder | Inheritance | Polyp type | Cancer risk | Extra clues |
|---|---|---|---|---|
| FAP (APC) | AD | Adenomatous (premalignant) | ~100% without colectomy | Desmoids, osteomas, CHRPE, duodenal adenomas |
| Lynch (HNPCC) | AD | Few/no polyps; right-sided tumors | High | Endometrial/ovarian cancers; DNA mismatch repair defects; MSI |
| Peutz-Jeghers | AD | Hamartomatous | Increased (various organs) | Mucocutaneous pigmentation, intussusception |
| Juvenile polyposis | AD | Hamartomatous | Increased CRC risk | Kids with painless bleeding, SMAD4/BMPR1A |
Rapid-fire USMLE pearls (memorize these)
- APC mutation → ↑ β-catenin → adenomas
- AD inheritance
- Hundreds to thousands of adenomatous polyps
- CRC risk ~100% without colectomy (often by age 40)
- Gardner = FAP + desmoids + osteomas + epidermoid cysts + CHRPE
- Duodenal/periampullary adenomas remain a major risk even after colon surgery
- NSAIDs reduce polyps but are not definitive prevention
Mini self-check (60 seconds)
- Teen with innumerable colon polyps + dad died of colon cancer at 35 → FAP (APC)
- Mechanism most tied to polyp formation → loss of APC → accumulation of β-catenin
- Best prevention of CRC → prophylactic colectomy
- Post-colectomy surveillance target → duodenum/periampullary region